The gram-negative enterobacterium Xenorhabdus nematophila mutualistically colonizes the intestines of S. carpocapsae infective juvenile nematodes. The objective of this project is a structural and functional analysis of X. nematophila Nil A, B and C membrane proteins that are required for colonization of S. carpocapsae. We hypothesize that Nil A, B and C function as a signal transduction complex, and will test this by examining interactions between the Nil proteins and other X. nematophila proteins, by determining whether the Nil proteins regulate gene expression in X. nematophila, and by deciphering the external signals recognized by the Nil proteins. Understanding molecular events underlying this model mutualistic interaction is relevant to understanding how microbes cause disease and for developing disease therapies. This statement is based on several findings: that pathogens and mutualists share common aspects in their interactions with hosts, that vertebrates and invertebrates share common aspects of immunity, which can be targeted for disease therapy, and finally, that beneficial microbes contribute to the overall health and life-styles of animals.